The Neonatal Fc receptor (FcRn) enhances human immunodeficiency virus type 1 (HIV-1) transcytosis across epithelial cells.

The mechanisms by which human immunodeficiency virus type 1 (HIV-1) crosses mucosal surfaces to establish infection are unknown. Acidic genital secretions of HIV-1-infected women contain HIV-1 likely coated by antibody. We found that the combination of acidic pH and Env-specific IgG, including that...

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Autores principales:	Sandeep Gupta, Johannes S Gach, Juan C Becerra, Tran B Phan, Jeffrey Pudney, Zina Moldoveanu, Sarah B Joseph, Gary Landucci, Medalyn Jude Supnet, Li-Hua Ping, Davide Corti, Brian Moldt, Zdenek Hel, Antonio Lanzavecchia, Ruth M Ruprecht, Dennis R Burton, Jiri Mestecky, Deborah J Anderson, Donald N Forthal
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/fc81d5d35a084780ba7fe91dd2ceb47a
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spelling	oai:doaj.org-article:fc81d5d35a084780ba7fe91dd2ceb47a2021-11-18T06:07:18ZThe Neonatal Fc receptor (FcRn) enhances human immunodeficiency virus type 1 (HIV-1) transcytosis across epithelial cells.1553-73661553-737410.1371/journal.ppat.1003776https://doaj.org/article/fc81d5d35a084780ba7fe91dd2ceb47a2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24278022/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374The mechanisms by which human immunodeficiency virus type 1 (HIV-1) crosses mucosal surfaces to establish infection are unknown. Acidic genital secretions of HIV-1-infected women contain HIV-1 likely coated by antibody. We found that the combination of acidic pH and Env-specific IgG, including that from cervicovaginal and seminal fluids of HIV-1-infected individuals, augmented transcytosis across epithelial cells as much as 20-fold compared with Env-specific IgG at neutral pH or non-specific IgG at either pH. Enhanced transcytosis was observed with clinical HIV-1 isolates, including transmitted/founder strains, and was eliminated in Fc neonatal receptor (FcRn)-knockdown epithelial cells. Non-neutralizing antibodies allowed similar or less transcytosis than neutralizing antibodies. However, the ratio of total:infectious virus was higher for neutralizing antibodies, indicating that they allowed transcytosis while blocking infectivity of transcytosed virus. Immunocytochemistry revealed abundant FcRn expression in columnar epithelia lining the human endocervix and penile urethra. Acidity and Env-specific IgG enhance transcytosis of virus across epithelial cells via FcRn and could facilitate translocation of virus to susceptible target cells following sexual exposure.Sandeep GuptaJohannes S GachJuan C BecerraTran B PhanJeffrey PudneyZina MoldoveanuSarah B JosephGary LanducciMedalyn Jude SupnetLi-Hua PingDavide CortiBrian MoldtZdenek HelAntonio LanzavecchiaRuth M RuprechtDennis R BurtonJiri MesteckyDeborah J AndersonDonald N ForthalPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 9, Iss 11, p e1003776 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Sandeep Gupta Johannes S Gach Juan C Becerra Tran B Phan Jeffrey Pudney Zina Moldoveanu Sarah B Joseph Gary Landucci Medalyn Jude Supnet Li-Hua Ping Davide Corti Brian Moldt Zdenek Hel Antonio Lanzavecchia Ruth M Ruprecht Dennis R Burton Jiri Mestecky Deborah J Anderson Donald N Forthal The Neonatal Fc receptor (FcRn) enhances human immunodeficiency virus type 1 (HIV-1) transcytosis across epithelial cells.
description	The mechanisms by which human immunodeficiency virus type 1 (HIV-1) crosses mucosal surfaces to establish infection are unknown. Acidic genital secretions of HIV-1-infected women contain HIV-1 likely coated by antibody. We found that the combination of acidic pH and Env-specific IgG, including that from cervicovaginal and seminal fluids of HIV-1-infected individuals, augmented transcytosis across epithelial cells as much as 20-fold compared with Env-specific IgG at neutral pH or non-specific IgG at either pH. Enhanced transcytosis was observed with clinical HIV-1 isolates, including transmitted/founder strains, and was eliminated in Fc neonatal receptor (FcRn)-knockdown epithelial cells. Non-neutralizing antibodies allowed similar or less transcytosis than neutralizing antibodies. However, the ratio of total:infectious virus was higher for neutralizing antibodies, indicating that they allowed transcytosis while blocking infectivity of transcytosed virus. Immunocytochemistry revealed abundant FcRn expression in columnar epithelia lining the human endocervix and penile urethra. Acidity and Env-specific IgG enhance transcytosis of virus across epithelial cells via FcRn and could facilitate translocation of virus to susceptible target cells following sexual exposure.
format	article
author	Sandeep Gupta Johannes S Gach Juan C Becerra Tran B Phan Jeffrey Pudney Zina Moldoveanu Sarah B Joseph Gary Landucci Medalyn Jude Supnet Li-Hua Ping Davide Corti Brian Moldt Zdenek Hel Antonio Lanzavecchia Ruth M Ruprecht Dennis R Burton Jiri Mestecky Deborah J Anderson Donald N Forthal
author_facet	Sandeep Gupta Johannes S Gach Juan C Becerra Tran B Phan Jeffrey Pudney Zina Moldoveanu Sarah B Joseph Gary Landucci Medalyn Jude Supnet Li-Hua Ping Davide Corti Brian Moldt Zdenek Hel Antonio Lanzavecchia Ruth M Ruprecht Dennis R Burton Jiri Mestecky Deborah J Anderson Donald N Forthal
author_sort	Sandeep Gupta
title	The Neonatal Fc receptor (FcRn) enhances human immunodeficiency virus type 1 (HIV-1) transcytosis across epithelial cells.
title_short	The Neonatal Fc receptor (FcRn) enhances human immunodeficiency virus type 1 (HIV-1) transcytosis across epithelial cells.
title_full	The Neonatal Fc receptor (FcRn) enhances human immunodeficiency virus type 1 (HIV-1) transcytosis across epithelial cells.
title_fullStr	The Neonatal Fc receptor (FcRn) enhances human immunodeficiency virus type 1 (HIV-1) transcytosis across epithelial cells.
title_full_unstemmed	The Neonatal Fc receptor (FcRn) enhances human immunodeficiency virus type 1 (HIV-1) transcytosis across epithelial cells.
title_sort	neonatal fc receptor (fcrn) enhances human immunodeficiency virus type 1 (hiv-1) transcytosis across epithelial cells.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/fc81d5d35a084780ba7fe91dd2ceb47a
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The Neonatal Fc receptor (FcRn) enhances human immunodeficiency virus type 1 (HIV-1) transcytosis across epithelial cells.

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